Rybelsus vs Jardiance (and Farxiga): GLP-1 tablet or SGLT2 inhibitor

Rybelsus and Jardiance are both once-daily tablets for type 2 diabetes, but they belong to different classes and have different strengths in the evidence. Rybelsus contains semaglutide, a GLP-1 receptor agonist that copies a gut hormone¹. Jardiance contains empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, the same class as dapagliflozin (Farxiga in the US, Forxiga in the UK and EU)⁴⁵. In PIONEER 2, the head-to-head trial, Rybelsus 14 mg lowered HbA1c more than empagliflozin 25 mg at 26 weeks, with similar weight loss¹. SGLT2 inhibitors are licensed for heart failure and chronic kidney disease as well as diabetes; Rybelsus is not⁴⁵¹. Guidelines use both classes, sometimes together, and the choice belongs with your prescriber¹⁵.

In the US, the newer 1.5, 4 and 9 mg Rybelsus tablets are now sold as Ozempic tablets¹⁷. See the Ozempic pill.

Rybelsus vs Jardiance vs Farxiga at a glance

Two different ways of lowering blood sugar

Semaglutide copies GLP-1 (glucagon-like peptide-1), a hormone the gut releases after eating. It makes the pancreas release more insulin and less glucagon when blood sugar is raised, and slightly slows how quickly the stomach empties¹. Because its effect on insulin depends on blood sugar being high, its risk of hypoglycaemia (low blood sugar) is low unless it is combined with insulin or a sulfonylurea¹².

Empagliflozin and dapagliflozin belong to a separate class, the SGLT2 inhibitors. They are taken as one tablet a day with no food rules⁴⁵.

That difference in routine matters day to day. Rybelsus has to be swallowed on an empty stomach with up to 120 ml of plain water, followed by at least 30 minutes with no food, drink or other tablets¹. The UK and EU labels also recommend fasting for at least 8 hours before the dose²³. See how to take Rybelsus.

PIONEER 2: the head-to-head trial

PIONEER 2 compared Rybelsus 14 mg with empagliflozin 25 mg in 822 adults with type 2 diabetes who were already taking metformin¹. At 26 weeks, in the US label's treatment-policy analysis (which counts everyone who started treatment, including people who stopped):

• HbA1c, a blood test that reflects average blood sugar over recent months, fell by 1.3 points with Rybelsus and 0.9 points with empagliflozin¹.
• Weight fell by 3.8 kg with Rybelsus and 3.7 kg with empagliflozin, a similar amount¹.

These figures cover blood sugar and weight only. Heart and kidney evidence for each medicine comes from separate trials, described below.

For context outside the head-to-head trial: on its own, empagliflozin lowered HbA1c by 0.7 (10 mg) and 0.9 (25 mg) points more than placebo over 24 weeks, with weight changes of -2.8% and -3.2% against -0.4%⁴. In PIONEER 1 (26 weeks, compared with placebo), Rybelsus lowered HbA1c by 1.2 (7 mg) and 1.4 (14 mg) points against 0.3¹. Those are separate trials and should not be compared directly.

Heart and kidney outcomes: what each class has shown

A hazard ratio compares the rate of events between two groups; below 1 means fewer events in the group on the trial medicine.

Empagliflozin. In the EMPA-REG OUTCOME trial in people with type 2 diabetes, cardiovascular death occurred in 3.7% on empagliflozin and 5.9% in the comparison group, a 38% relative reduction; the hazard ratio for major cardiovascular events was 0.86⁸. In the US it is licensed to reduce cardiovascular death in adults with type 2 diabetes and established cardiovascular disease, and for heart failure and chronic kidney disease⁴.

Dapagliflozin. DECLARE-TIMI 58 did not reduce major cardiovascular events, but lowered the combined risk of cardiovascular death or hospitalisation for heart failure (hazard ratio 0.83)⁹. Its dedicated trials in heart failure with reduced ejection fraction (a weakened heart pump), DAPA-HF, and in chronic kidney disease, DAPA-CKD, reported hazard ratios of 0.74 and 0.61 for their main outcomes¹⁰¹¹. It is licensed for heart failure and chronic kidney disease in the US, EU and UK⁵⁷.

Rybelsus. SOUL followed 9,650 adults aged 50 or over with type 2 diabetes and atherosclerotic cardiovascular disease (heart or circulation disease caused by narrowed arteries), chronic kidney disease or both, for an average of 47.5 months, comparing oral semaglutide (up to 14 mg) with placebo on top of standard care. Major cardiovascular events (cardiovascular death, non-fatal heart attack or non-fatal stroke) happened to 12.0% vs 13.8%, a hazard ratio of 0.86¹². This led to a US cardiovascular risk reduction indication on 17 October 2025; in the EU and UK the results are in the product information without a separate indication¹⁶³². SOUL's kidney composite outcome was not significantly different (hazard ratio 0.91)¹². Semaglutide's kidney-outcome evidence comes from the FLOW trial of the weekly injection, Ozempic, not the tablet¹³; see Rybelsus vs Ozempic.

Each trial had its own population, length and comparison group, so the percentages cannot be set side by side.

What each is licensed for, and where guidelines place them

• Rybelsus: adults with type 2 diabetes. In the US, also cardiovascular risk reduction in adults at high risk. In the UK and EU, on its own only when metformin is unsuitable, otherwise with other diabetes medicines. Not licensed for weight loss or for heart failure or kidney disease¹²³.
• Jardiance and Farxiga (US): type 2 diabetes in adults and children aged 10 and over, heart failure and chronic kidney disease, plus the cardiovascular indications in the table above⁴⁵.
• Jardiance and Forxiga (EU and UK): type 2 diabetes, heart failure and chronic kidney disease⁶⁷.

NICE guideline NG28 recommends modified-release metformin plus an SGLT2 inhibitor as initial therapy for most adults with type 2 diabetes, and recommends injected semaglutide for people with atherosclerotic cardiovascular disease¹⁴. The American Diabetes Association's 2026 Standards of Care recommend an SGLT2 inhibitor and/or a GLP-1 receptor agonist for people with atherosclerotic cardiovascular disease regardless of HbA1c, and an SGLT2 inhibitor for people with heart failure; they list cardiovascular benefit for injected and oral semaglutide¹⁵. Generic dapagliflozin is listed in the UK¹⁸. For Rybelsus costs, see Rybelsus price.

Side effects: stomach upset vs genital infections

Rybelsus. The most common side effects are nausea, abdominal pain, diarrhoea, decreased appetite, vomiting and constipation¹. In placebo-controlled trials, nausea affected 20% on 14 mg against 6% on placebo, and 8% on 14 mg stopped because of stomach side effects against 1%¹. Vomiting and diarrhoea can lead to dehydration and acute kidney injury, so drink fluids and contact a healthcare professional if they are severe or do not settle¹. See Rybelsus side effects.

SGLT2 inhibitors. Genital fungal infections (thrush) are a recognised side effect of empagliflozin and dapagliflozin⁴⁵. Diabetic ketoacidosis, a serious complication in which acids build up in the blood, is rare: in DECLARE-TIMI 58 it occurred in 0.3% on dapagliflozin against 0.1%⁹.

Low blood sugar. The UK and EU Rybelsus product information list hypoglycaemia as common (1 in 100 to 1 in 10 people) when Rybelsus is used with other oral diabetes medicines, and very common with insulin or a sulfonylurea²³. Ask your pharmacist what to watch for with your combination.

Can Rybelsus and an SGLT2 inhibitor be used together?

The UK and EU licences allow Rybelsus to be used with other diabetes medicines²³, and the ADA's "SGLT2 inhibitor and/or GLP-1 receptor agonist" wording means guidelines allow either class or both¹⁵. PIONEER 2 compared the two rather than combining them, so its results do not describe what happens when both are taken¹. Whether a combination fits you is your prescriber's decision.

If you do take both, the Rybelsus timing rule still applies: take Rybelsus first on an empty stomach and wait at least 30 minutes before any other tablet, including an SGLT2 inhibitor¹. Do not stop, start or change a diabetes medicine without speaking to your prescriber. See also Rybelsus vs metformin.